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81.
The influence of material property and morphological parameters on specimen-specific finite element models of porcine vertebral bodies 总被引:4,自引:0,他引:4
Wilcox RK 《Journal of biomechanics》2007,40(3):669-673
The use of finite element (FE) methods in spinal research is increasing, but there is only limited information available on the influence of different input parameters on the model predictions. The aim of this study was to investigate the role of these parameters in FE models of the vertebral body. Experimental tests were undertaken on porcine lumbar vertebral bodies and scans of the specimens were used to create specimen-specific FE models. Three models were created for each specimen with combinations of generic and specimen-specific parameters. Stiffness and strength predictions were also made directly from the specimen trabecular bone volume fraction (BVF) and cross-sectional area (CSA). The agreement between the experimental results and the FE models with generic morphology was poorer (concordance coefficients = 0.058, 0.125 for stiffness, strength) than those made from the BVF and CSA (concordance coefficients = 0.638, 0.609). The greatest levels of agreement were found with the morphologically specific models including element-specific material properties (concordance coefficients = 0.881, 0.752). This indicates that highly specific models, both in terms of morphology and bone quality, are necessary if the FE tool is to be used effectively for spinal research and clinical practice. 相似文献
82.
Palm F Onozato ML Luo Z Wilcox CS 《American journal of physiology. Heart and circulatory physiology》2007,293(6):H3227-H3245
Asymmetric (N(G),N(G))-dimethylarginine (ADMA) inhibits nitric oxide (NO) synthases (NOS). ADMA is a risk factor for endothelial dysfunction, cardiovascular mortality, and progression of chronic kidney disease. Two isoforms of dimethylarginine dimethylaminohydrolase (DDAH) metabolize ADMA. DDAH-1 is the predominant isoform in the proximal tubules of the kidney and in the liver. These organs extract ADMA from the circulation. DDAH-2 is the predominant isoform in the vasculature, where it is found in endothelial cells adjacent to the cell membrane and in intracellular vesicles and in vascular smooth muscle cells among the myofibrils and the nuclear envelope. In vivo gene silencing of DDAH-1 in the rat and DDAH +/- mice both have increased circulating ADMA, whereas gene silencing of DDAH-2 reduces vascular NO generation and endothelium-derived relaxation factor responses. DDAH-2 also is expressed in the kidney in the macula densa and distal nephron. Angiotensin type 1 receptor activation in kidneys reduces the expression of DDAH-1 but increases the expression of DDAH-2. This rapidly evolving evidence of isoform-specific distribution and regulation of DDAH expression in the kidney and blood vessels provides potential mechanisms for nephron site-specific regulation of NO production. In this review, the recent advances in the regulation and function of DDAH enzymes, their roles in the regulation of NO generation, and their possible contribution to endothelial dysfunction in patients with cardiovascular and kidney diseases are discussed. 相似文献
83.
Brian S. Roberts Andrew A. Hardigan Marie K. Kirby Meredith B. Fitz-Gerald C.?Mel Wilcox Robert P. Kimberly Richard M. Myers 《Nucleic acids research》2015,43(21):e145
Highly abundant microRNAs (miRNAs) in small RNA sequencing libraries make it difficult to obtain efficient measurements of more lowly expressed species. We present a new method that allows for the selective blocking of specific, abundant miRNAs during preparation of sequencing libraries. This technique is specific with little off-target effects and has no impact on the reproducibility of the measurement of non-targeted species. In human plasma samples, we demonstrate that blocking of highly abundant hsa-miR-16–5p leads to improved detection of lowly expressed miRNAs and more precise measurement of differential expression overall. Furthermore, we establish the ability to target a second abundant miRNA and to multiplex the blocking of two miRNAs simultaneously. For small RNA sequencing, this technique could fill a similar role as do ribosomal or globin removal technologies in messenger RNA sequencing. 相似文献
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Peter?M.?RabinowitzEmail author Zimra?Gordon Rebecca?Holmes Brynn?Taylor Matthew?Wilcox Daniel?Chudnov Prakash?Nadkarni F.?Joshua?Dein 《EcoHealth》2005,2(1):26-37
Despite recognition that animals could be serving as sentinels for environmental risks to human health, there are no evidence-based guidelines for the use of animal sentinel data in human health
decision making. We performed a systematic review of the animal sentinel literature to assess the evidence linking such events to human health. A search of MEDLINE identified peer-reviewed original studies of animals as sentinels for either chemical or biological environmental hazards. A limited search of the CAB and AGRICOLA databases was also performed. We classified a random sample of 100 studies from the MEDLINE search according to species, hazard, and health outcome examined; study methods; and linkages to human health. Animal sentinel studies were difficult to locate in MEDLINE because of a lack of adequate key words for this concept. We found significant limitations in the study methods used to investigate animal sentinel events. Clear linkages to human health were frequently absent. Studies of sentinel events in animal populations hold potential for the recognition and control of human environmental health hazards, yet a number of barriers exist to using such data for evidence-based human health decisions. There is a need for greater data sharing and cooperative research between human and animal health professionals regarding environmental hazards and health outcomes in animal and human populations. 相似文献
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Wilcox A Katsanakis KD Bheda F Pillay TS 《The Journal of biological chemistry》2004,279(37):38881-38888
The APS adapter protein plays a pivotal role in coupling the insulin receptor to CAP and c-Cbl in the phosphatidylinositol 3-kinase-independent pathway of insulin-stimulated glucose transport. Yeast two-hybrid screening of a 3T3-L1 adipocyte library using APS as a bait identified a 418-amino acid ankyrin and SOCS (suppressor of cytokine signaling) box protein Asb6 as an interactor. Asb6 is an orphan member of a larger family of Asb proteins that are ubiquitously expressed. However, Asb6 expression appears to be restricted to adipose tissue. Asb6 was specifically expressed in 3T3-L1 adipocytes as a 50-kDa protein but not in fibroblasts. In Chinese hamster ovary-insulin receptor (CHO-IR) cells Myc epitope-tagged APS interacted constitutively with FLAG-tagged Asb6 in the presence or absence of insulin stimulation and insulin stimulation did not alter the interaction. In 3T3-L1 adipocytes, insulin receptor activation was accompanied by the APS-dependent recruitment of Asb6. Asb6 did not appear to undergo tyrosine phosphorylation. Immunofluorescence and confocal microscopy studies revealed that Asb6 colocalized with APS in CHO cells and in 3T3-L1 adipocytes. In immunoprecipitation studies in CHO cells or 3T3-L1 adipocytes, the Elongin BC complex was found to be bound to Asb6, and activation of the insulin receptor was required to facilitate Asb6 recruitment along with Elongins B/C. Prolonged insulin stimulation resulted in the degradation of APS when Asb6 was co-expressed but not in the absence of Asb6. We conclude that Asb6 functions to regulate components of the insulin signaling pathway in adipocytes by facilitating degradation by the APS-dependent recruitment of Asb6 and Elongins BC. 相似文献
90.
Mutations in TRIOBP, which encodes a putative cytoskeletal-organizing protein, are associated with nonsyndromic recessive deafness
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Riazuddin S Khan SN Ahmed ZM Ghosh M Caution K Nazli S Kabra M Zafar AU Chen K Naz S Antonellis A Pavan WJ Green ED Wilcox ER Friedman PL Morell RJ Riazuddin S Friedman TB 《American journal of human genetics》2006,78(1):137-143
In seven families, six different mutant alleles of TRIOBP on chromosome 22q13 cosegregate with autosomal recessive nonsyndromic deafness. These alleles include four nonsense (Q297X, R788X, R1068X, and R1117X) and two frameshift (D1069fsX1082 and R1078fsX1083) mutations, all located in exon 6 of TRIOBP. There are several alternative splice isoforms of this gene, the longest of which, TRIOBP-6, comprises 23 exons. The linkage interval for the deafness segregating in these families includes DFNB28. Genetic heterogeneity at this locus is suggested by three additional families that show significant evidence of linkage of deafness to markers on chromosome 22q13 but that apparently have no mutations in the TRIOBP gene. 相似文献